A virus in the blood or not? ME/CFS researchers in Nijmegen en America are quarreling over it.

by: Ellen Visser

In recent months the U.S. findings on the relationship between chronic fatigue syndrome (CFS) and a retro-virus were refuted by three European studies. Yet, remarkably enough, the American research caused international blood banks to take measures. Earlier this month, the Canadian organization in charge of the blood supply decided to exclude all patients who were suffering or had suffered from ME/CFS from donating blood.

Australia and New Zealand are considering the same step. European organizations are deliberating, a spokesman for the Dutch Sanquin stated.

'The scientific evidence is thin indeed, but we want to keep our blood as safe as possible.'

'Incomprehensible', says Jos van der Meer, professor of internal medicine at Nijmegen University. After the American Whittemore-Peterson Institute (WPI) had found the XMRV virus in two thirds of a group of CFS patients and had published their findings in Science, Van der Meer and his colleagues repeated the study. They found nothing. Earlier two British research groups had come to the same conclusion.

But the publication of the Dutch study in the British Medical Journal two months ago did not resolve the matter. WPI is behaving 'extremely unprofessional', says Van der Meer, by treating everybody who criticizes the American results in a very aggressive manner. The decision of the blood banks adds extra fuel to the flames.

Two weeks ago WPI director Annette Whittemore sent a letter to the British Professor of Retrovirology Myra McClure. McClure had not found the virus in the blood of CFS patients, and Whittemore invited her to exchange blood samples. She wondered whether the professor had used the right techniques for finding the virus. In the letter, that was published on the site of the WPI, Whittemore wiped the floor with the Dutch study. As it turned out WPI had indeed exchanged blood samples with the Nijmegen researchers and out of ten Dutch samples the Americans identified three samples that tested positive.

Furthermore, the Nijmegen researchers had received positive American samples in order to check whether they were able to find the XMRV virus. However, in their published paper the Dutch team kept silent about all of this.

Van der Meer calls it 'extremely unscientific' that the integrity of his research team was questioned in a letter to another party. This week Nijmegen sent a letter back to the WPI (which was also published on their (Nijmegens) website).

'It is true that we have sent blood samples to the WPI', he explains. 'The Americans have detected the virus in two of the seven samples that were taken from patients, and in one of three samples from a control group. That means a score of 30% for both groups, in other words: no difference in incidence between patients and controls. We postponed publication and retested the three samples but they remained negative. We saw no reason to readjust our publication.'

The Nijmegen team did find XMRV in the positive samples that the WPI had sent to them. In addition they were able to detect the virus in the positive cell line of prostate cancer that was sent to them by the Nijmegen urology laboratory. 'Therefore it cannot be that our method was not right. Moreover, we have used the same method as the Americans have.'

International researchers have written letters to Science about the methodological shortcomings of the U.S. study. The letter that Nijmegen sent was accepted. Research should have taken place in at least two different laboratories, Van der Meer says. 'When you work with a particular virus regularly there is a risk that you contaminate your own samples. In the case of positive test results, especially when they are very important, any scientist knows you never should rely on one laboratory, I don't understand that Science agreed to that.'

Van der Meer says he has proposed to the WPI to exchange complete sets of samples. 'There is still no response.' Research by, among others, the American CDC's should clarify who is right. The U.S. Department of Health is currently investigating whether XMRV can be transmitted by blood. For the time being, CFS patients can give blood, according to the CDC's website.

The question is whether people are doing this, Van der Meer says. Perhaps they are already banned because a good health is a prerequisite for donating blood. Moreover, the last thing CFS patients would want for themselves is to lower their blood hemoglobin, he says. 'I would discourage patients to donate blood'.

It seems to me that Vad der Meer is "extremely unprofessional". You send your samples to another institute which checks it with their methods and find some of the samples positives (it does not matter if these samples are from patients or controls. even if they were all from controls - it does not matter. and by the way, even with just PCR in the first study, WPI found 3.7% of to control group to have XMRV. Anyway, the only thing that metters is that their tests were able to find XMRV in these samples), you check them again - find nothing, and then continue with your study and publish it without mention a word about the same samples being found positive at the WPI. Now, when you sent the samples to the WPI, what did you think? Did you think: "well, if they cannot find anything I can publish that even WPI didn't find anything, and if they do find something I would just not publish that they found something"? I mean, did you actually think that was not gonna be found out?

Now, the second thing is, and here I don't know if I'm somehow wrong (and tell me if I am, but I think I'm not), but the WPI did use the services of other laboratory or laboratories who checked their samples (I don't know if the same ones or other samples) and confirmed their finding. So why mentioning "Any scientist known you never should rely on one laboratory, I don't understand that Science agreed to that"?

Besides: I tend to believe Dr. Mikovits, Dr. Peterson, Dr. Lombardi, Dr. Coffin, Dr. Ruscetti, the professionals in the cleveland clinic, the professionals in the National Cancer Institute, the professionals in "Science" and all the others who said good stuff about this study (John Coffin: "For a first paper it's as good as it gets"), than to believe some "scientists" who says it all in our heads and sends us to do CBT.

But you know what? It's turning my stomach. It's turning my stomach because I can't tell for sure that these "scientists" like Van der Meer and his friends won't win this battle; And it's turning my stomach that even if it would be proven beyond any reasonable doubt that XMRV is related to ME/CFS, these so-called scientists won't get their punishment from a court of law.

(...)Did you think: "well, if they cannot find anything I can publish that even WPI didn't find anything, and if they do find something I would just not publish that they found something"? I mean, did you actually think that was not gonna be found out?(...)

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I think that they went out from the first assumption. They took 20 year old samples from patients diagnosed with the Oxford (Wessely) criteria and thought that even WPI would find nothing in this small amount of samples, which contained (I think) a lot of samples of just depressed people.
I think that they were shocked by the fact that WPI did find something with their smarter techniques, and didn't know what to do... and just went for the only escape that was left: "we found nothing so WPI must have had contamination problems"

and about the one lab fable: test results of WPI were confirmed by two independent labs (NCI and Cleveland Clinic) so there were three labs involved in the Science study.
But Van der Meer tells this Rubbish to the papers in The Netherlands en people who know nothing about ME/CFS just believe it. Volkskrant is relatively a quality paper in The Netherlands.

And Van der Meer is Chairman of the "gezondheidsraad", which is the main advising board in The Netherlands of dutch ministers and the parlement about medical issues...
in other words he is mega influential here

There are two significant omissions in that paper: 1) they did not mention a reported discrepancy in results; 2) they did not mention that they used a blood sample from WPI as a positive control, though they stated this to the press. The second omission is critical to validation of their implementation of the test for XMRV. This may be the only case in those three negative studies where blood drawn from an actual patient, already known to be infected, tested positive. Other positive controls came from cultures using cloned (PC?) cell lines.

Even the Japanese group seeking to detect XMRV in prostate cancer, where the diagnostic criteria are not in question, admitted they had trouble getting positive results until they followed suggestions from WPI. Unless paying attention to WPI mentally contaminates laboratories in other countries, this indicates XMRV is difficult to find, and WPI knows how.

One other really obvious inference seems to have escaped notice, the samples sent to WPI were only labeled 1-7. Three were from controls, so four must have been from CFS patients. Though the numbers are too small to be statistically significant, it appears WPI correctly identified half the CFS samples, under difficult conditions, even with lousy diagnostic criteria. If they can do any better than chance at identifying patients based on nothing except blood samples drawn from those patients and stored for 20 years, something they are doing, no matter how screwed up, is a lead to a biomarker. All the Nijmegen group had to do was keep sending blinded samples to find out if WPI was onto something or was simply guessing.

This group was clearly not interested in pursuing such a lead. Their behavior in breaking off communication with a curt note neatly foreclosed the possibility of further cooperation.

And Van der Meer is Chairman of the "gezondheidsraad", which is the main advising board in The Netherlands of dutch ministers and the parlement about medical issues...
in other words he is mega influential here

I have copied below a post by Revotril from the '1st XMRV international conference on XMRV' thread. I also find it worrying that the organiser of the US XMRV conference is presenting alongside van der Meer in the Netherlands in June.

He is not a retrovirologist and promotes the psychosocial model of ME. What could he possibly contribute to this meeting? Perhaps this question should be put to Mr Boucher.

Besides, this company also arranges a meeting about infectious diseases in The Netherlands on June 4th, where one of the members of the organisation board of the XMRV workshop in the USA (Charles Boucher) will presentate about XMRV along with Van der Meer, The co-author of The Dutch XMRV study:

This has been mentioned in passing, but I don't recall it all put together.

By measures everyone agrees about, WPI got 4 out of 7 blinded samples correct, two positive and two negative. If they knew the ratio of controls to CFS patients in the group, they could have done this by flipping a coin. Were they told? I don't think so.

How many of the errors are due to diagnostic criteria? We have read that 36% of the subjects with CFS were diagnosed as clinically depressed by experienced doctors, presumably psychiatrists. Psychiatrists are pretty reliable at diagnosing clinical depression, they see a lot of it. When their diagnoses fail, it is more likely to be a false negative than false positive.

We have also read that 32% of subjects reported they did not feel particularly depressed, implying 68% did complain of depression. With over half diagnosed as clinically depressed this is actually on the low side. Far more people believe they are "depressed" than suffer the horror of the real, life-threatening clinical illness. (I am using the term horror deliberately. Horror writer H.P. Lovecraft fought a long battle with depression. Subjectively, he probably did experience some of those lurid nightmares he wrote about.)

By the published criteria of the experimental protocol, it is not at all unlikely that 50% of the CFS subjects were suffering from primary psychiatric illness without infection. This would account for 6 out of 7 samples.

The remaining false positive from a control could be a chance finding of an infection elsewhere indicated in 4% of the general population, but it doesn't have to be. In order to match socio-economic status and geographic location, researchers often choose controls from the same household, or neighbors. The primary criterion was that they seemed healthy, and did not complain of fatigue. Researchers were not concerned about asymptomatic carriers of an infection transmitted by contact. Had they been looking for an infectious disease, this would have been a serious flaw. Clearly, they were not.

Possible interpretation of WPI test results could range from 4 out of 7 correct to all 7 blinded samples correctly identified. The Nijmegen group have not falsified any hypothesis about CFS and infection, except concerning their own lab's ability to detect, and might have unwittingly uncovered supporting evidence. Under these circumstances, blaming results from three other laboratories on contamination, without elaboration, is pure hubris.

Defense of their "well-defined cohort" takes us in another direction. It looks very much as if the original experimental design was structured in such a way that a pure psychiatric hypothesis is not falsifiable. For those unfamiliar with research, any hypothesis which is not falsifiable is not acceptable science, though it may certainly be a matter of faith.

I have copied below a post by Revotril from the '1st XMRV international conference on XMRV' thread. I also find it worrying that the organiser of the US XMRV conference is presenting alongside van der Meer in the Netherlands in June.

He is not a retrovirologist and promotes the psychosocial model of ME. What could he possibly contribute to this meeting? Perhaps this question should be put to Mr Boucher.

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Another question raisening point to me, is the the subject of the Dutch Debate:een nieuw retrovirus (XMRV) bij de mens: passagier of pathogeen?
Prof. dr. Jos van der Meer
Prof. dr. Charles Boucher

Translated in English this means: A new human Retrovirus (XMRV): passenger or pathogene?

This subject may give raise to the thought that, the next step of the Nijmegen School can be, this:
When there is, at a later time, consensus about the appearance of XMRV in ME/CFS patients (e.g. when there are some real replication studies done, which support the WPI-paper), Nijmegen will switch to plan B and argue that XMRV is not the cause, but just another passenger in ME/CFS (like other opportunistic infections found in ME/CFS patients).

I think that they will do anything to minimize the importance of XMRV, and, according to the title of the debate, maybe they're already planning their route (if plan A (XMRV doesn't appear at all in ME/CFS patients) fails, we have already a plan B).

But, June is not too far away, so we will soon know what the man really has to tell us about XMRV

This is the overview of the meeting, courtesy of Google almost-Translate.

The field of infectious diseases is in continuous motion, we are dealing with (un-) expected epidemics, there appear new antimicrobial agents on the market and develop into resistant micro-organisms. We also develop new research and we get a better understanding of the pathogenesis. Given these dynamics, we organize on June 4th. a national meeting in order to allow researchers and practitioners the latest developments in an interactive way to share and the possible implications for patient care to discuss.

Major Findings in infectious diseases will be a workshop format with plenary presentations, question and answers sessions, roundtable discussions and a debate. The meeting is financially sponsored by Pfizer eg.

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As Revotril says, the debate in question is titled "A new retrovirus (XMRV) in humans: passenger or pathogen?". Only Boucher and van der Meer are down as taking part in this. Perhaps they will be debating with each other, or perhaps with the audience, or perhaps with another speaker yet to be confirmed.

I can see why van der Meer may want to participate in the debate (see Revotril's plan B, above) but find it odd that he should be invited/included in a meeting about infectious pathogens when he does not believe one of these may cause ME and has little knowledge of such microbes. It is even stranger that he, and not van Kuppeveld, is attending given that the latter is the retrovirologist **.

I note that cost of attendance (including coffee breaks and lunch) is 35 Euros. Is anyone in the Netherlands able to go?

Regarding the Plan B...If it was indeed opportunistic, wouldn't that mean that nearly everybody in the population would have been already in contact with it and developped antibodies? CFSers would simply be not be able to keep it bay anymore. If that's not the case and a much smaller population of healthy subjects shows sign of past XMRV exposure, then it's most likely not opportunistic. Right?

The idea of a retrovirus being a simple passenger seems far fetched to me...Well even if it's passenger for whatever reasons, do you want something messing with your DNA taking the ride or do you treat it...?

Regarding the Plan B...If it was indeed opportunistic, wouldn't that mean that nearly everybody in the population would have been already in contact with it and developped antibodies?

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I fully agree with you gu3vara, and this is also one of the first things Nancy Klimas said about XMRV after the Science paper appeared. see:http://www.youtube.com/watch?v=pXMTXhqb3n8
from 1.37 she makes the point that the passenger theory/ comparison with opportunistic infections may not really be plausible

We will have to wait for further announcements and actions from Nijmegen, but I expect that they will continue their strange actions. Giving up the XMRV issue is for them just giving up their jobs, careers, and the end of their psychosocial approach, so that's no option for them, at any circumstances

Hopefully, they will continue to fight, as this will more likely discredited them much more quickly. Coffin, Ruscetti and others, are of such importance, that the media will be forced to shine a light on their lies and incompetence. It will be a major story for years to come, and we will finally have respect, treatments, and a cure. :victory:

Nijmegen will switch to plan B and argue that XMRV is not the cause, but just another passenger in ME/CFS (like other opportunistic infections found in ME/CFS patients).

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The good news is that we can still expect to be treated for it, even if the psychiatrists fantasize that we magically evoked it in ourselves through our "inappropriate illness beliefs." If xmrv turns out to be implicated as the puppetmaster, we can expect treating it to aid us.